Evaporative light scattering detectors (ELSDs) are used routinely for Liquid Chromatography (LC) analysis. In an ELSD, a liquid sample is converted to droplets by a nebulizer. As the droplets traverse a drift tube, the solvent portion of the droplets evaporates, leaving less volatile analyte. The sample passes to a detection cell, where light scattering of the sample is measured. ELSDs can be used for analyzing a wide variety of samples.
The present inventors identify the nebulizer as a limit on the effectiveness of the detection capabilities of ELSDs. One problem with conventional nebulizers is that complete solvent evaporation does not occur in the drift tube. The expanding trajectory and variable sizes of the droplets produced by conventional nebulizers contributes to the incomplete evaporation and erratic measurement performance. Droplets enter the detection cell and cause scattering that is detected. The scatter effect of droplets is indicated in conventional ELSDs by the fact that substantial scattering is detected in the absence of analytes. This droplet scattering creates a large level of background noise. Accordingly, with typical ELSDs, it is only possible to measure differential scattering, where scattering from the analyte is much greater than that from incompletely volatilized solvent droplets.
Droplets that are too small to carry sufficient analyte are also produced within the distribution of droplets produced by a conventional nebulizer. The small droplets result in analyte particles that are too small to contribute to the detection signal. However, the small droplets increase solvent vapor pressure in the drift tube. Higher vapor pressure retards evaporation in the drift tube. Incomplete evaporation leads to the background noise from scattering caused by droplets as discussed above.
If the droplet size distributions and evaporation rate were constant in the conventional ELSD nebulizers, then the resultant background noise could, to a certain degree, be accounted for in the measurement. However, the rate of incomplete droplet vaporization and their distribution (size and number) tends to change randomly with time. This causes uncertainty in the analyte signal, in addition to the substantial level of background noise.
One conventional strategy for addressing the droplet distribution problem of conventional nebulizers is to remove larger droplets. An impactor has been used in the drift tube of conventional ELSDs to intercept large droplets, which are collected and exit the drift tube through an outlet drain. Additional condensation collects on the walls of the drift tube due to the divergence of spray from the nebulizer, and also drains from the outlet drain. A percentage of the divergent spray that exits via the outlet drain includes properly sized droplets with analyte. Excluding larger droplets produced by a conventional nebulizer proves difficult in practice because the nature of the droplet distribution depends strongly on three factors: mobile phase composition, mobile phase flow rate and carrier gas flow rate. The dependence is highly interactive, which makes the spray hard to control and difficult to model. These undesirable nebulizer characteristics place extraordinary demands on the structural design of ELSD units, making their design very complicated and highly empirical.